The tumor immune microenvironment plays a critical role in cancer progression and response to immunotherapy in clear cell renal cell carcinoma (ccRCC), yet the composition and phenotypic states of immune cells in this tumor are incompletely characterized. We performed single-cell RNA and T cell receptor sequencing on 164,722 individual cells from tumor and adjacent non-tumor tissue in patients with ccRCC across disease stages: early, locally advanced, and advanced/metastatic. Terminally exhausted CD8 T cells were enriched in metastatic disease and were restricted in T cell receptor diversity. Within the myeloid compartment, pro-inflammatory macrophages were decreased, and suppressive M2-like macrophages were increased in advanced disease. Terminally exhausted CD8 T cells and M2-like macrophages co-occurred in advanced disease and expressed ligands and receptors that support T cell dysfunction and M2-like polarization. This immune dysfunction circuit is associated with a worse prognosis in external cohorts and identifies potentially targetable immune inhibitory pathways in ccRCC.Copyright © 2021 Elsevier Inc. All rights reserved.
About The Expert
David A Braun
Kelly Street
Kelly P Burke
David L Cookmeyer
Thomas Denize
Christina B Pedersen
Satyen H Gohil
Nicholas Schindler
Lucas Pomerance
Laure Hirsch
Ziad Bakouny
Yue Hou
Juliet Forman
Teddy Huang
Shuqiang Li
Ang Cui
Derin B Keskin
John Steinharter
Gabrielle Bouchard
Maxine Sun
Erica M Pimenta
Wenxin Xu
Kathleen M Mahoney
Bradley A McGregor
Michelle S Hirsch
Steven L Chang
Kenneth J Livak
David F McDermott
Sachet A Shukla
Lars R Olsen
Sabina Signoretti
Arlene H Sharpe
Rafael A Irizarry
Toni K Choueiri
Catherine J Wu
References
PubMed